All this time, if change happens in cell genome which controls the expression or the function in cell growth and cell differentiation, it is considered as the major cause inducing tumor. Molecular biology study in tumor is directed to confirm those changes of genes in various tumor types and to illustrate the functions of these genes in tumorigenesis. In particular, RAS gene is one of the most common gene families in tumor mutation of human.
Under normal physiology circumstances, when a signaling pathway such as EGFR is activated after cells are stimulated by the external, the wild-type KRAS is phosphorylated by a tyrosine kinase such as active EGFR, before being transiently activated. The activated KRAS can activate the downstream signaling protein in the signaling pathway, after that the KRAS is inactivated rapidly. The activation/inactivation effect of the KRAS is controllable. However, mutant KRAS protein causes a dysfunction of protein that the mutant KRAS is still under activated status without the stimulation of activation signal from EGFR, such that the functional status of mutant KRAS is uncontrollable which makes the tumors proliferate continuously. The RAS gene, like a “switch” in vivo, plays an important regulating role in the signal transduction path of processes such as tumor cell growth and angiogenesis. The encoded protein of normal KRAS gene can inhibit tumor cell growth. Once the KRAS gene mutates, it will continuously stimulate the cell growth, disorganize the growth rhythm and thus cause tumorigenesis. Because the mutation of the KRAS gene generally occurs at the early stage of the tumor malignancy, also the KRAS genes of the primary tumor and the metastases are highly consistent; and it is generally acknowledged that the status of KRAS gene will not change with the treatment. Therefore, the detection of the mutation in the KRAS gene is an important indicator for in-depth understanding of the condition of oncogene as well as the development, prognosis and the curative effect of the chemoradiotherapy for various cancers, having a vitally important clinical significance.
In China, pancreatic cancer has always been one of the top ten malignant tumors that causing the population death, having a five-year survival rate of less than 5%, being one of the worst malignant tumors in prognosis. In recent years, colorectal cancer has become the second biggest cancer killer in Guangdong area with obviously increasing trend, having a morbidity and a mortality that significantly increase year by year. The RAS gene of tumor cells has a mutation rate of about 25% while pancreatic cancer, colorectal cancer and non-small alveolar lung cancer have a mutation rate of 90%, 45% and 35%, respectively.
In late 1970s and early 1980s, a disease with a dysfunction of the immune system as a major characteristic arose in Europe and the United States. Afterwards, scientists from various countries started to explore the nosogenesis and the therapeutic schedule for such disease. Until 1983, after the Pasteur Research Group in France first successfully isolated this new retrovirus, the theoretical study and the medical treatment for HIV-1 became more and more. Nowadays, medicine against HIV-1 mainly acts on different stages of the life cycle of the virus, and specifically on some necessary enzymes such as reverse transcriptase and protease.
Although there are many anti-HIV-1 medicines that are commercial available nowadays and HARRT is widely used, the resulting problems such as drug resistance, huge medical expenses and the side effects of the medicines should not be underestimated. Plasma viral load in a considerable number of patients can be reduced below a detectable level by highly active antiretroviral therapy (HARRT), but the rebound after stopping taking such medicine and the severe toxic side effects are still can't be solved. Gene therapy has shown its potential for anti-virus and some research achievement has entered clinical test stage, but its low efficiency and the adverse reaction possibly brought by the foreign vector are still the major obstacle to research and development. Nowadays, there are four major hot spots for the research and development of anti-HIV-1 medicine internationally: 1) inhibitor that inhibits virus entering into the cells; 2) neutralizing antibody; 3) integrase inhibitor; and 4) chemical chemokine receptor antagonists. Scientists still keep trying to explore an anti-virus medicine that is safer, more effective and more affordable.
Regulator of expression of virion proteins (Rev) is an indispensable regulatory protein in the transcription process of HIV-1. The Rev interacts with RRE of mRNA of the virus so as to aid unspliced or partially spliced mRNA of HIV-1 to transfer out of the nucleus. If the expression of the Rev is inhibited, the unspliced or partially spliced mRNA of HIV-1 will be unable to transfer out of the nucleus, leading to a complete degradation within the nucleus, and a further block of the replication of HIV-1. Therefore, how to inhibit the expression of Rev protein will be an important target for research and development of anti-HIV-1 medicine.